Research in the Pharmacological Sciences Center addresses the biosynthesis, metabolism, function and pharmacology of eicosanoids and related biologically active compounds. The scientists in the Center include clinical pharmacologists working in close association with biochemical pharmacologists as well as analytical and organic chemists. The release of prostaglandin D2 as a mast cell mediator in clinical disorders including asthma is being investigated in conjunction with studies on the metabolism of prostaglandin D2 to a series of compounds that possess biological activity. The participation of eicosanoids in the pathophysiology of allergic asthma is being assessed. Several lines of investigation address the mechanism whereby aspirin and other cyclooxygenase inhibitors trigger bronchoconstriction and systemic mastocyte activation. The mechanisms and characteristics of the abnormalities in eicosanoid biosynthesis in cigarette smokers are being evaluated in relationship to the dysfunction of platelets and the vessel wall. Lipoxygenase pathways of arachidonic acid are being examined with particular emphasis upon those reactions that are initiated by abstraction of hydrogen at carbon-lO of arachidonic acid. The investigations within the Center are conducted in conjunction with the development of new methods for quantifying arachidonic acid metabolites and related compounds utilizing stable isotope dilution approaches with mass spectrometry. The development of approaches for assessing the production of arachidonic acid metabolites in man enables the rational investigation of new and old drugs that may act on this system.